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Cell Rep. 2014 Sep 25;8(6):1677-1685. doi: 10.1016/j.celrep.2014.08.039. Epub 2014 Sep 18.

A cell engineering strategy to enhance the safety of stem cell therapies.

Author information

1
Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2
Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
3
Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
4
Mouse Genetics Core, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
5
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
6
Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
7
Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
8
Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: wendelh@mskcc.org.

Abstract

The long-term risk of malignancy associated with stem cell therapies is a significant concern in the clinical application of this exciting technology. We report a cancer-selective strategy to enhance the safety of stem cell therapies. Briefly, using a cell engineering approach, we show that aggressive cancers derived from human or murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are strikingly sensitive to temporary MYC blockade. On the other hand, differentiated tissues derived from human or mouse iPSCs can readily tolerate temporary MYC inactivation. In cancer cells, endogenous MYC is required to maintain the metabolic and epigenetic functions of the embryonic and cancer-specific pyruvate kinase M2 isoform (PKM2). In summary, our results implicate PKM2 in cancer's increased MYC dependence and indicate dominant MYC inhibition as a cancer-selective fail-safe for stem cell therapies.

PMID:
25242333
PMCID:
PMC4177332
DOI:
10.1016/j.celrep.2014.08.039
[Indexed for MEDLINE]
Free PMC Article

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